Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries

NCT ID: NCT04288245

Last Updated: 2023-09-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-15

Study Completion Date

2025-04-30

Brief Summary

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Texas Biomedical Device Center at UT Dallas has developed an innovative strategy to enhance recovery of motor and sensory function after neurological injury termed targeted plasticity therapy (TPT). This technique uses brief pulses of vagus nerve stimulation to engage pro-plasticity neuromodulatory circuits during rehabilitation exercises. Recovery is associated with neural plasticity in spared motor networks in the brain and spinal cord. Moreover, an early feasibility study and an independent, double-blind, placebo-controlled study in chronic stroke participants indicate that VNS is safe in participants with upper limb deficits, and yields a clinically-significant three-fold increase in neural connections during rehabilitation exercises. Given the track record of safety and potential for VNS to enhance recovery of upper limb motor function in spinal cord injured individuals, the purpose of this double blind randomized placebo controlled optional open-label extension study is to assess the safety of using a new device to deliver vagus nerve stimulation to reduce symptom severity in participants with SCI. Additionally, the study will assess the prospective benefit of the system and garner an initial estimate of efficacy for a subsequent trial. Participants may undergo additional sessions of training with VNS.

Detailed Description

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Conditions

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Spinal Cord Injuries Upper Extremity Paresis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Double blind, randomized placebo controlled, optional open-label extension design
Primary Study Purpose

DEVICE_FEASIBILITY

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Immediate Start Vagus Nerve Stimulation group

The Immediate Start VNS group will receive rehabilitation and active stimulation for 18 in-office sessions over the course of approximately 6 weeks during phase 1. For phase 2, all subjects will be provided the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.

Group Type EXPERIMENTAL

Active Vagus Nerve Stimulation

Intervention Type DEVICE

Stimulation of the vagus nerve that is paired with upper extremity rehabilitation. VNS stimulation as described in the current study consists of 0.5 s trains of 0.8 mA 100 µs biphasic pulses delivered at 30 Hz. Stimulation trains are delivered only during rehabilitation.

Delayed Start Vagus Nerve Stimulation group

The Delayed Start VNS group will receive equivalent rehabilitation with placebo stimulation for 18 in-office sessions over the course of approximately 6 weeks during phase 1. For phase 2, all subjects will be provided the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.

Group Type PLACEBO_COMPARATOR

Placebo Vagus Nerve Stimulation

Intervention Type DEVICE

During Phase 1 of the study, the placebo group will receive a minimal amount of stimulation that fails to sufficiently activate the nerve, unknown to the participant and therapists. All participants will receive active stimulation during the Phase 2 open-label portion of the study.

Interventions

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Active Vagus Nerve Stimulation

Stimulation of the vagus nerve that is paired with upper extremity rehabilitation. VNS stimulation as described in the current study consists of 0.5 s trains of 0.8 mA 100 µs biphasic pulses delivered at 30 Hz. Stimulation trains are delivered only during rehabilitation.

Intervention Type DEVICE

Placebo Vagus Nerve Stimulation

During Phase 1 of the study, the placebo group will receive a minimal amount of stimulation that fails to sufficiently activate the nerve, unknown to the participant and therapists. All participants will receive active stimulation during the Phase 2 open-label portion of the study.

Intervention Type DEVICE

Other Intervention Names

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VNS vagus nerve stimulation paired VNS placebo control

Eligibility Criteria

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Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Adult, aged 18-64
* In good general health as evidenced by medical history and diagnosed with first time cervical spinal cord injury resulting in an ASIA grade B, C, or D, and level 1 or better motor function as described by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).
* SCI caused by trauma that occurred ≥ 12 months prior to enrollment
* Meets all clinical criteria for the surgical VNS implantation as determined by the PI, surgeon, and anesthesiologist
* Must demonstrate some residual upper limb and hand movement in either arm
* Appropriate candidate for VNS implantation
* Willing and able to comply with the study protocol

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

* Spinal cord injuries by sharp objects, firearms, and non-traumatic or congenital causes, even if at different levels of the spinal cord
* Any evidence of recurrent laryngeal nerve injury (Evident during required laryngoscopy for all participants with Prior right-sided anterior cervical surgery- done prior to randomization)
* Excessive scar tissue marking implantation unsafe (evident at surgery)
* Concomitant clinically significant brain injuries
* Prior injury to vagus nerve
* Prior or current treatment with vagus nerve stimulation
* Participant receiving any therapy (medication or otherwise) that would interfere with VNS
* Pregnancy or lactation
* Clinical complications that hinder or contraindicate the surgical procedure
* Psychiatric disorders, psychosocial, and/or cognitive impairment that would interfere with study participation, as assessed by medical evaluation
* Abusive use of alcohol and/or illegal substances use
* Participation in other interventional clinical trial
* Participants with known immunodeficiency including participants who are receiving or have received chronic corticosteroids, immunosuppressants, immunostimulating agents or radiation therapy within 6 months
* Significant comorbidities or conditions associated with high risk for surgical or anesthetic survival (e.g. renal failure, peripheral vascular disease, unstable cardiac disease, poorly controlled diabetes, immunosuppression, etc.).
* Active neoplastic disease.
* Participants with significant local circulatory problems, (e.g. thrombophlebitis and lymphedema).
* Participants with any medical condition or other circumstances that might interfere with their ability to return for follow-up visits in the judgment of the Investigator, including systemic illness, neuromuscular, neurosensory, or musculoskeletal deficiency that would render the participant unable to perform appropriate postoperative rehabilitation.
* Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance.
* Aphasia and other cognitive deficits that make understanding the potential risks and benefits of the study impossible for participant. Inability to personally provide informed consent.
* A recent history of syncope
* A recent history of dysphagia
* Currently require, or are likely to require diathermy
* Significant respiratory issues that would interfere with participation
* Non-English speaking
* Patients who are acutely suicidal and/or have been admitted for a suicide attempt
* Incarceration or legal detention
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wings for Life

OTHER

Sponsor Role collaborator

Defense Advanced Research Projects Agency

FED

Sponsor Role collaborator

The University of Texas at Dallas

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

Baylor Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Kilgard, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas at Dallas

Robert Rennaker, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas at Dallas

Seth Hays, PhD

Role: STUDY_DIRECTOR

University of Texas at Dallas

Jane Wigginton, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Rita Hamilton, DO

Role: PRINCIPAL_INVESTIGATOR

Baylor Scott & White Institute for Rehabilitation

Michael Foreman, MD FACS

Role: STUDY_DIRECTOR

Baylor Health Care System

Mark Powers, PhD

Role: STUDY_DIRECTOR

Baylor Health Care System

Richard Naftalis, MD, FAANS, FACS

Role: STUDY_DIRECTOR

Baylor Health Care System

Locations

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Baylor University Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Alvaro Carrera

Role: CONTACT

469-831-5321

Facility Contacts

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Alvaro Carrera

Role: primary

469-831-5321

References

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Biering-Sorensen F, Bryden A, Curt A, Friden J, Harvey LA, Mulcahey MJ, Popovic MR, Prochazka A, Sinnott KA, Snoek G. International spinal cord injury upper extremity basic data set. Spinal Cord. 2014 Sep;52(9):652-7. doi: 10.1038/sc.2014.87. Epub 2014 Jun 3.

Reference Type BACKGROUND
PMID: 24891012 (View on PubMed)

Catz A, Itzkovich M, Tesio L, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J. A multicenter international study on the Spinal Cord Independence Measure, version III: Rasch psychometric validation. Spinal Cord. 2007 Apr;45(4):275-91. doi: 10.1038/sj.sc.3101960. Epub 2006 Aug 15.

Reference Type BACKGROUND
PMID: 16909143 (View on PubMed)

Corson K, Gerrity MS, Dobscha SK. Screening for depression and suicidality in a VA primary care setting: 2 items are better than 1 item. Am J Manag Care. 2004 Nov;10(11 Pt 2):839-45.

Reference Type BACKGROUND
PMID: 15609737 (View on PubMed)

Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP, Borland MS, Kilgard MP. Reversing pathological neural activity using targeted plasticity. Nature. 2011 Feb 3;470(7332):101-4. doi: 10.1038/nature09656. Epub 2011 Jan 12.

Reference Type BACKGROUND
PMID: 21228773 (View on PubMed)

Hays SA, Rennaker RL, Kilgard MP. Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog Brain Res. 2013;207:275-99. doi: 10.1016/B978-0-444-63327-9.00010-2.

Reference Type BACKGROUND
PMID: 24309259 (View on PubMed)

Itzkovich M, Gelernter I, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J, Catz A. The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 2007 Dec 30;29(24):1926-33. doi: 10.1080/09638280601046302. Epub 2007 Mar 5.

Reference Type BACKGROUND
PMID: 17852230 (View on PubMed)

Jebsen RH, Taylor N, Trieschmann RB, Trotter MJ, Howard LA. An objective and standardized test of hand function. Arch Phys Med Rehabil. 1969 Jun;50(6):311-9. No abstract available.

Reference Type BACKGROUND
PMID: 5788487 (View on PubMed)

Kalsi-Ryan S, Beaton D, Curt A, Duff S, Popovic MR, Rudhe C, Fehlings MG, Verrier MC. The Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity. J Neurotrauma. 2012 Mar 20;29(5):905-14. doi: 10.1089/neu.2010.1504. Epub 2011 Aug 12.

Reference Type BACKGROUND
PMID: 21568688 (View on PubMed)

Kirshblum SC, Burns SP, Biering-Sorensen F, Donovan W, Graves DE, Jha A, Johansen M, Jones L, Krassioukov A, Mulcahey MJ, Schmidt-Read M, Waring W. International standards for neurological classification of spinal cord injury (revised 2011). J Spinal Cord Med. 2011 Nov;34(6):535-46. doi: 10.1179/204577211X13207446293695. No abstract available.

Reference Type BACKGROUND
PMID: 22330108 (View on PubMed)

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

Reference Type BACKGROUND
PMID: 11556941 (View on PubMed)

Widerstrom-Noga E, Biering-Sorensen F, Bryce TN, Cardenas DD, Finnerup NB, Jensen MP, Richards JS, Siddall PJ. The International Spinal Cord Injury Pain Basic Data Set (version 2.0). Spinal Cord. 2014 Apr;52(4):282-6. doi: 10.1038/sc.2014.4. Epub 2014 Jan 28.

Reference Type BACKGROUND
PMID: 24469147 (View on PubMed)

Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

Reference Type BACKGROUND
PMID: 6880820 (View on PubMed)

Kilgard MP, Epperson JD, Adehunoluwa EA, Swank C, Porter AL, Pruitt DT, Gallaway HL, Stevens C, Gillespie J, Arnold D, Powers MB, Hamilton RG, Naftalis RC, Foreman ML, Wigginton JG, Hays SA, Rennaker RL. Closed-loop vagus nerve stimulation aids recovery from spinal cord injury. Nature. 2025 Jul;643(8073):1030-1036. doi: 10.1038/s41586-025-09028-5. Epub 2025 May 21.

Reference Type DERIVED
PMID: 40399668 (View on PubMed)

Other Identifiers

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N66001-17-2-4011

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

019-356

Identifier Type: -

Identifier Source: org_study_id

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